Subchronic Toxicity of Green Algae (Spyrogyra SP.) Ethanolic Extract on Hematologic Parameters

Green Algae, an organism with active substance such as phytomelatonin, has potential to be developed as Indonesian traditional medicine. As the long term addition of Green Algae ethanol extract (Ekstrak etanol ganggang hijau, EEGH) influences the hematology system, in this paper, the safety test was done to ensure the safety of its use through subchronic toxicity test of EEGH on the hematology parameters of Wistar rats. The test group consisted of three groups treated with EEGH 100 mg/kg, 200 mg/kg, and 400 mg/kg, while the control group was given by 0.5% CMC-Na, with 8 rats each respectively. By using blood samples taken from orbital sinus on the 29th day, common hematologic parameters (erythrocytes, leukocytes, and hemoglobin level), the parameters of hemostasis (platelets, pT, aPTT, BT) and immune parameters (Differential Leukocytes Counts include neutrophils segment, lymphocytes, monocytes, and eosinophils) were finally observed and showed that the 28 days-addition of EEGH increase the hematological parameters of Wistar rats

Study of Acute Toxicity of a New Veterinary Drug for Inttrammary Introduction

Preclinical studies of veterinary medicinal products are important and compulsory studies in the development of new dosage forms. The aim of preclinical research is to determine the toxic effect and therapeutic efficacy of the test substance-the future dosage form, its effect on the body\u27s basic systems, as well as the identification of possible side effects.This work is part of the research on the development of the composition and technology of the veterinary drug - a solution for intramammary application, conventionally called "Argocide", intended for the treatment of mastitis in cattle.A study of the acute toxicity of the intramammary veterinary drug was carried out in experiments on white rats of both sexes, according to the requirements for potential medicines. The establishment of the value of the average lethal dose (LD50) of the veterinary drug "Argocide" with intramuscular single administration to white mature rats is impossible due to the absence of animal death even when the drug is administered at doses exceeding 5.0 ml/kg. This experiment allows the veterinary preparation "Argocide" to be classified as practically non-toxic compounds (V class).The analysis of the results of the conducted studies indicates the relative harmlessness of the potential drug for veterinary medicine and allows us to foresee that the "Argocide" preparation can be classified as low-risk substances, which justifies the expediency of its further study and introduction into practice

FGF-2 Induces Neuronal Death through Upregulation of System xc-

The cystine/glutamate antiporter (system xc-) transports cystine into cell in exchange for glutamate. Fibroblast growth factor-2 (FGF-2) upregulates system xc- selectively on astrocytes, which leads to increased cystine uptake, the substrate for glutathione production, and increased glutamate release. While increased intracellular glutathione can limit oxidative stress, the increased glutamate release can potentially lead to excitotoxicity to neurons. To test this hypothesis, mixed neuronal and glial cortical cultures were treated with FGF-2. Treatment with FGF-2 for 48 h caused a significant neuronal death in these cultures. Cell death was not observed in neuronal-enriched cultures, or astrocyte-enriched cultures, suggesting the toxicity was the result of neuron-glia interaction. Blocking system xc- eliminated the neuronal death as did the AMPA/kainate receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX), but not the NMDA receptor antagonist memantine. When cultures were exposed directly to glutamate, both NBQX and memantine blocked the neuronal toxicity. The mechanism of this altered profile of glutamate receptor mediated toxicity by FGF-2 is unclear. The selective calcium permeable AMPA receptor antagonist 1-naphthyl acetyl spermine (NASPM) failed to offer protection. The most likely explanation for the results is that 48 h FGF-2 treatment induces AMPA/kainate receptor toxicity through increased system xc- function resulting in increased release of glutamate. At the same time, FGF-2 alters the sensitivity of the neurons to glutamate toxicity in a manner that promotes selective AMPA/kainate receptor mediated toxicity

High dose rate brachytherapy as monotherapy for localised prostate cancer : a hypofractionated two-implant approach in 351 consecutive patients

BACKGROUND: To report the clinical outcome of high dose rate brachytherapy as sole treatment for clinically localised prostate cancer. METHODS: Between March 2004 and January 2008, a total of 351 consecutive patients with clinically localised prostate cancer were treated with transrectal ultrasound guided high dose rate brachytherapy. The prescribed dose was 38.0 Gy in four fractions (two implants of two fractions each of 9.5 Gy with an interval of 14 days between the implants) delivered to an intraoperative transrectal ultrasound real-time defined planning treatment volume. Biochemical failure was defined according to the Phoenix Consensus and toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 3. RESULTS: The median follow-up time was 59.3 months. The 36 and 60 month biochemical control and metastasis-free survival rates were respectively 98%, 94% and 99%, 98%. Toxicity was scored per event with 4.8% acute Grade 3 genitourinary and no acute Grade 3 gastrointestinal toxicity. Late Grade 3 genitourinary and gastrointestinal toxicity were respectively 3.4% and 1.4%. No instances of Grade 4 or greater acute or late adverse events were reported. CONCLUSIONS: Our results confirm high dose rate brachytherapy as safe and effective monotherapy for clinically organ-confined prostate cancer

Validating the chronic Pb algae bioavailability model at high pH : single-species evaluation : final report, 12 June 2017

We investigated toxicity of Pb to Pseudokirchneriella subcapitata using the standard 72h-growth inhibition assays at 2 pH levels (pH 7.2 & pH 8.4) and 2 P (P 10 ug/L & P 100 ug/L) levels, i.e. at 4 treatments in total. This was done to test whether an existing algae Pb bioavailability model developed for pH≤8.0, can be used at higher pH>8.0. The algae Pb bioavailability model calibrated on Pb toxicity at pH 7.2 (P 100 µg/L) predicted filtered Pb toxicity(EC50 and EC20) at pH 8.4 (P 100 µg/L) with reasonable accuracy, i.e. within 2-fold error. Although the slope of the linear relationship between pH and log10(EC50 as Pb2+ acitivity) for the pH range between 7.2 and 8.4 (present study) was slightly lower than that of the pH range between 6 and 8 (existing model), our study suggests that the chronic algae Pb bioavailability model can be extrapolated to predict Pb toxicity up to pH 8.4

Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial

Carboplatin/taxane combination is first-line therapy for ovarian cancer. However, patients can encounter treatment delays, impaired quality of life, even death because of chemotherapy-induced gastrointestinal (GI) toxicity. A candidate gene study was conducted to assess potential association of genetic variants with GI toxicity in 808 patients who received carboplatin/taxane in the Scottish Randomized Trial in Ovarian Cancer 1 (SCOTROC1). Patients were randomized into discovery and validation cohorts consisting of 404 patients each. Clinical covariates and genetic variants associated with grade III/IV GI toxicity in discovery cohort were evaluated in replication cohort. Chemotherapy-induced GI toxicity was significantly associated with seven single-nucleotide polymorphisms in the ATP7B, GSR, VEGFA and SCN10A genes. Patients with risk genotypes were at 1.53 to 18.01 higher odds to develop carboplatin/taxane-induced GI toxicity (P<0.01). Variants in the VEGF gene were marginally associated with survival time. Our data provide potential targets for modulation/inhibition of GI toxicity in ovarian cancer patients

Toxicity of Pb and of Pb/Cd combination on the springtail Folsomia candida in natural soils: Reproduction, growth and bioaccumulation as indicators

The toxicity of Pb and Cd+Pb was assessed on the Collembola F. candida in two cultivated soils (SV and AU) with low organic matter (OM) content and circumneutral to basic pH, and an acid forested soil (EPC) with high OM content. Collembola reproduction and growth as well as metal content in Collembola body, in soil, exchangeable fraction and soil solutions, pH and DOC were investigated. Pb and Cd+Pb were the highest in exchangeable fraction and soil solution of the acidic soils. Soil solution pH decreased after metal spiking in every soil due to metal adsorption, which was similar for Cd and the highest in AU for Pb. With increasing Pb and Cd+Pb, the most important reproduction decrease was in EPC soil. The LOEC for reproduction after metal addition was 2400 (Pb) and 200/2400 (Cd/Pb), 1200 and 100/1200, 300 and 100/1200 μg g−1 for AU, SV and EPC, respectively. The highest and the lowest Pb toxicity was observed for EPC and AU bulk soil, respectively. The metal in Collembola increased with increasing soil concentration, except in AU, but the decreasing BFsolution with increasing concentrations indicates a limited metal transfer to Collembola or an increased metal removal. Loading high Pb concentrations decreases Cd absorption by the Collembola, but the reverse was not true. The highest Pb toxicity in EPC can be explained by pH and OM content. Because of metal complexation, OM might have a protective role but its ingestion by Collembola lead to higher toxicity. Metal bioavailability in Collembola differs from soil solution indicating that soil solution is not sufficient to evaluate toxicity in soil organisms. The toxicity as a whole decreased when metals were combined, except for Pb in AU, due to adsorption competition between Cd and Pb on clay particles and OM sites in AU and EPC soils, respectively

Acute toxicity of synyhetic resin effluent to African Catfish, Clarias gariepinus [BURCHELL, 1822].

Aquatic pollution as a field has gained a lot of attention over the decades majorly because of the vital role the aquatic environment plays in the human lifecycle. Indusrial wastewaters are often generated and discharged into the environment without treatment. Toxicity of effluents from Synythetic Resin production plant were evaluated in this study. Acute toxicity (96-h LC50) was evaluated using 0.23, 0.31, 0.35 and 0.39 mg/L of the effluent in a renewal bioassay procedure. Physicochemical parameters of the effluent were also evaluated, the values obtained for lead, cyanide, total suspened solid, total hadness, total dissolved solids and alkalinity were higher than the Federal Environmental Protection Agency standard specification for effluent discharge into aquatic environment and as such contributed to the effluent's toxicity. Mortality increased as the concentrations of the effluent increases and 0.355mg/L was obtained as LC50. The research eventually revealed that the synthetic resin effluent has a high level of toxicity to catfish. Deleterious effects such as biomagnification and other abberations may occur in man if exposed to substantial concentration of the effluent

Poison Frog Colors Are Honest Signals Of Toxicity, Particularly For Bird Predators

Antipredator defenses and warning signals typically evolve in concert. However, the extensive variation across taxa in both these components of predator deterrence and the relationship between them are poorly understood. Here we test whether there is a predictive relationship between visual conspicuousness and toxicity levels across 10 populations of the color-polymorphic strawberry poison frog, Dendrobates pumilio. Using a mouse-based toxicity assay, we find extreme variation in toxicity between frog populations. This variation is significantly positively correlated with frog coloration brightness, a viewer-independent measure of visual conspicuousness (i.e., total reflectance flux). We also examine conspicuousness from the view of three potential predator taxa, as well as conspecific frogs, using taxon-specific visual detection models and three natural background substrates. We find very strong positive relationships between frog toxicity and conspicuousness for bird-specific perceptual models. Weaker but still positive correlations are found for crab and D. pumilio conspecific visual perception, while frog coloration as viewed by snakes is not related to toxicity. These results suggest that poison frog colors can be honest signals of prey unpalatability to predators and that birds in particular may exert selection on aposematic signal design.Integrative Biolog